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SRP073608
Mus musculus
24 Downloadable Samples
Illumina HiSeq 2500
Description
Aging is a key factor in Alzheimer''s disease, but it''s correlation with the pathology and pathological factors like amyloid-beta remains unclear In our study we aimed to provide an extensive characterisation of age-related changes in the gene expression profile of APP23 mice and controls and correlate these changes to pathological and symptomatic features of the model We found a clear biphasic expression profile with a developmental and aging phase. The second phase, particularly, displays aging features and similarties with the progression of Alzheimer pathology in human patients Processes involved in microglial activation, lysosomal processing, neuronal differantion and cytoskeletal regulation appear key factors in this stage. Interestingly, the changes in the gene expression profile of APP23 mice also seem to occur in control animals, but at a later age. The changes appear accelerated and/or exacerbated in APP23 mice. Overall design: mRNA profiles of APP23 mice and wild-type control littermates aged 1.5, 6, 18 or 24 months. For all the age groups, samples of 3 mice of each genotype were analyzed
Publication Title
Aging, microglia and cytoskeletal regulation are key factors in the pathological evolution of the APP23 mouse model for Alzheimer's disease.
Sample Metadata Fields
Age, Specimen part, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Ion Torrent Proton
Description
We previously reported a pathogenic de novo W342 mutation in the transcriptional corepressor CtBP1 in four independent patients with neurodevelopmental disabilities. Here, we report the clinical phenotypes of seven additional individuals with the same recurrent de novo CtBP1 mutation. Within this cohort we identified consistent CtBP1-related phenotypes of intellectual disability, ataxia, hypotonia and tooth enamel defects present in all patients. The W342 mutation in CtBP1 is located within a region implicated in a high affinity-binding cleft for CtBP-interacting proteins. Unbiased proteomic analysis demonstrated reduced interaction of several chromatin modifying factors with the CtBP1 W342 mutant. Genome-wide transcriptome analysis in human glioblastoma cells lines expressing -CtBP1 R342 (wt) or W342 mutation revealed changes in the expression profiles of genes controlling multiple cellular processes. Patient-derived dermal fibroblasts were found to be more sensitive to apoptosis during acute glucose deprivation compared to controls. Glucose deprivation strongly activated the BH3-only pro-apoptotic gene NOXA, suggesting a link between enhanced cell death and NOXA expression in patient fibroblasts. Our results suggest that context-dependent relief of transcriptional repression of the CtBP1 mutant W342 allele may contribute to deregulation of apoptosis in target tissues of patients leading to neurodevelopmental phenotypes. Overall design: Total RNA samples were isolated from 3 different cultures of HTB17 cells that overexpressed CtBP1 wt or the pathogenic mutant, W342 and analyzed by high- throughput RNA sequencing.
Publication Title
A pathogenic CtBP1 missense mutation causes altered cofactor binding and transcriptional activity.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
mRNA expression in colon cancer tumores
Publication Title
Mice that express human interleukin-8 have increased mobilization of immature myeloid cells, which exacerbates inflammation and accelerates colon carcinogenesis.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 31 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The nuclear bile acid receptor FXR is a PKA- and FOXA2-sensitive activator of fasting hepatic gluconeogenesis.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 23 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Identified genes deregulated in mouse primary hepatocytes after modulation of expression/activity of FOXA2 and FXR in glucagon or insulin state
Publication Title
The nuclear bile acid receptor FXR is a PKA- and FOXA2-sensitive activator of fasting hepatic gluconeogenesis.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
The gene expression of murine splenic myeloid derived suppressor cells treated with Tff2 is characterized. The motivation of the study originates in the fact that Gr1+Cd11b+ myeloid-derived suppressor cells (MDSCs), which resemble immature myeloid cells (IMCs), expand during cancer in response to inflammatory cytokines and accumulate in the spleen. MDSCs promote neoplastic progression through their suppression of anti-tumourigenic cytotoxic T-cells. MDSCs are also rapidly expanded following acute insults, but in cancer as opposed to acute inflammation, MDSCs persist. It is now recognized that a vagally-mediated, anti-inflammatory reflex arc promoting acetylcholine secretion by Cd4+ (Cd44hiSelllo) T cells, is necessary for a return to homeostasis after an acute insult. Failure of this restorative neural circuit might contribute to unabated procarcinogenic inflammation, with the chronic expansion of MDSCs driving carcinogenesis. Trefoil factor 2 (Tff2) is a secreted anti-inflammatory peptide produced by both epithelial cells and a small subset of splenic T cell.
Publication Title
Neural innervation stimulates splenic TFF2 to arrest myeloid cell expansion and cancer.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Livers from wild-type (WT) or Ppara knock-out (Ppara KO) C57Bl6 mice were used to prepare RNA which was then processed for analysis using MoGene-2_0-st Affymetrix microarrays according to standard procedures.
Publication Title
The logic of transcriptional regulator recruitment architecture at <i>cis</i>-regulatory modules controlling liver functions.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Distinct regulatory mechanisms and functions for p53-activated and p53-repressed DNA damage response genes in embryonic stem cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The tumor suppressor p53 regulates the differentiation of embryonic stem (ES) cells upon DNA damage. However, our understanding of this critical tumor suppressive role of p53 in ES cells is limited, mainly because of the lack of molecular mechanism. Here, we report a widespread cross-regulation of p53-mediated DNA damage signaling and the pluripotent gene network in ES cells using chromatin-immunoprecipitation assay-based sequencing (ChIP-seq) and gene expression microarray. Upon DNA damage, p53 directly regulates the transcription of 3644 genes (p<0.005) in mouse ES cells. Genome-wide analysis revealed a dramatic difference between the regulation of p53-activated and -repressed genes. p53 mainly regulates the promoter regions of activated genes, whereas the main regulatory regions for repressed genes reside in distal regions. Among p53-repressed genes, many are pluripotent transcription factors of ES cells, such as Oct4, Nanog, Sox2, Esrrb, c-Myc, n-Myc and Sall4. Strikingly, these transcriptional factors also directly regulate the transcription of the Trp53 gene, highlighting a previously under-estimated transcriptional regulation of p53 in ES cells. Therefore, p53 signaling and ES pluripotent transcriptional networks form an intertwined circuitry. Together, our results provide mechanistic insights into the crosstalk of p53-mediated DNA damage and ES cell "stemness" transcriptional gene networks and shed light on the tumor suppressive function of p53 in ES cells.
Publication Title
Distinct regulatory mechanisms and functions for p53-activated and p53-repressed DNA damage response genes in embryonic stem cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Rattus norvegicus
- 91 Downloadable Samples
- Affymetrix Rat Genome U34 Array (rgu34a)
Description
Summary: The liver is the major site of gluconeogenesis, fat processing and distribution, as well as drug and xenobiotic metabolism. Altered gene expression in the liver is centrally invovled in both the immuosuppressive and the energetic actions of corticosteroids.
Publication Title
Modeling of corticosteroid pharmacogenomics in rat liver using gene microarrays.
Sample Metadata Fields
No sample metadata fields
View Samples